Abstract
Neural stem cells exist in the developing and adult nervous systems of all mammals, but the basic mechanisms that control their behavior are not yet well understood. Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells. We found high expression of the Shh receptor Patched in both the adult rat hippocampus and neural progenitor cells isolated from this region. In addition, Shh elicited a strong, dose-dependent proliferative response in progenitors in vitro. Furthermore, adeno-associated viral vector delivery of shh cDNA to the hippocampus elicited a 3.3-fold increase in cell proliferation. Finally, the pharmacological inhibitor of Shh signaling cyclopamine reduced hippocampal neural progenitor proliferation in vivo. This work identifies Shh as a regulator of adult hippocampal neural stem cells.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Division / drug effects
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Cell Division / genetics*
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Cells, Cultured
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Female
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Fluorescent Antibody Technique
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics
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Hedgehog Proteins
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Hippocampus / cytology
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Hippocampus / growth & development*
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Hippocampus / metabolism
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In Vitro Techniques
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Membrane Proteins / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Patched Receptors
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Rats
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Rats, Inbred F344
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Receptors, Cell Surface
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / genetics
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Trans-Activators / metabolism*
Substances
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Hedgehog Proteins
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Membrane Proteins
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Patched Receptors
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Receptors, Cell Surface
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Trans-Activators